@misc{MoradianRochLendleinetal.2020,
  author    = {Moradian, Hanieh and Roch, Toralf and Lendlein, Andreas and Gossen, Manfred},
  title     = {mRNA transfection-induced activation of primary human monocytes and macrophages},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51569},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-515694},
  pages     = {17},
  year      = {2020},
  abstract  = {Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.},
  language  = {en}
}
@article{MoradianRochLendleinetal.2020,
  author    = {Moradian, Hanieh and Roch, Toralf and Lendlein, Andreas and Gossen, Manfred},
  title     = {mRNA transfection-induced activation of primary human monocytes and macrophages},
  series = {Scientific reports},
  volume    = {10},
  journal   = {Scientific reports},
  number    = {1},
  publisher = {Springer Nature},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/s41598-020-60506-4},
  pages     = {1 -- 15},
  year      = {2020},
  abstract  = {Monocytes and macrophages are key players in maintaining immune homeostasis. Identifying strategies to manipulate their functions via gene delivery is thus of great interest for immunological research and biomedical applications. We set out to establish conditions for mRNA transfection in hard-to-transfect primary human monocytes and monocyte-derived macrophages due to the great potential of gene expression from in vitro transcribed mRNA for modulating cell phenotypes. mRNA doses, nucleotide modifications, and different carriers were systematically explored in order to optimize high mRNA transfer rates while minimizing cell stress and immune activation. We selected three commercially available mRNA transfection reagents including liposome and polymer-based formulations, covering different application spectra. Our results demonstrate that liposomal reagents can particularly combine high gene transfer rates with only moderate immune cell activation. For the latter, use of specific nucleotide modifications proved essential. In addition to improving efficacy of gene transfer, our findings address discrete aspects of innate immune activation using cytokine and surface marker expression, as well as cell viability as key readouts to judge overall transfection efficiency. The impact of this study goes beyond optimizing transfection conditions for immune cells, by providing a framework for assessing new gene carrier systems for monocyte and macrophage, tailored to specific applications.},
  language  = {en}
}
@article{WangNaolouMaetal.2017,
  author    = {Wang, Weiwei and Naolou, Toufik and Ma, Nan and Deng, Zijun and Xu, Xun and Mansfeld, Ulrich and Wischke, Christian and Gossen, Manfred and Neffe, Axel T. and Lendlein, Andreas},
  title     = {Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells},
  series = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  volume    = {18},
  journal   = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1525-7797},
  doi       = {10.1021/acs.biomac.7b01034},
  pages     = {3819 -- 3833},
  year      = {2017},
  abstract  = {The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M (n) similar to 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.},
  language  = {en}
}